The prevalence of the metabolic syndrome is increasing at alarming rates in the United States, even in the pediatric population. In this proposal, Dr. Biddinger, focusing on the liver, will examine the molecular links between insulin resistance, dyslipidemia and gallstones, three features of the metabolic syndrome, and how they are modified by dietary factors. These studies build on Dr. Biddinger's prior work examining the effects of diet and genetic background on hepatic lipid metabolism and gene expression, and the development of the metabolic syndrome. The primary goal of this mentored career development award is to provide a mechanism for Dr. Biddinger, a trained pediatric endocrinologist, to achieve scientific independence. By developing an expertise in lipid metabolism and microarray analysis, she will distinguish herself from her mentor, Dr. C. Ronald Kahn, and be well positioned to make significant scientific and medical contributions to the understanding of insulin resistance in children and adolescents.